Case Western Reserve University researchers and BioInVision, Inc. will develop a cryo-imaging system for 3D imaging of mice. It will serve applications in stem cell regenerative medicine, metastatic cancer, and pathogen/immune system response, among others. By alternately sectioning and imaging, the system will enable 1 to acquire 3D high-resolution color and fluorescence episcopic images. This system will image cells tagged with GFP, or other reporter genes which create fluorescent proteins. By imaging with high resolution and sensitivity, we will establish a method for identifying single or multiple tagged cells within a mouse. The system should enable identification of stem cells, micro-metastases, bacteria, lymphocytes, neurons, and other specialized tissues. Once cells are identified, cell locations can be mapped relative to the tissue anatomy in the high contrast, 3D color episcopic images. In addition, histological samples can be obtained for further characterization of the cellular microenvironment and stem cell differentiation. There are other potential applications in biological research and in the pharmaceutical industry, including mouse anatomical phenotype identification, drug evaluation, imaging agent evaluation, drug delivery evaluation, study of diseases, etc. Cryo-imaging is unique among all in vivo and microscopic techniques in that it allows micron resolution and information-rich contrast mechanisms over very large 3D fields of view. It will fill the gap between whole animal in vivo imaging and histology, allowing 1 to image a mouse along the continuum from the mouse -> organ -> tissue structure -> cell -> sub-cellular domains. We will develop an imaging system that lies within the continuum between in vivo small animal imaging and histology. This sytem will enable researchers to study in great detail where fluoresently tagged cells go in the body, how they change, and how they respond to their microenvironment. This will aid research in stem cell therapy, nerve cell development, immune response, and metastatic cancer, among others. This system will help researchers understand physiology and disease mechanisms and promote research for cures. [unreadable] [unreadable] [unreadable]